title: SNAI1 protein expression is an independent negative prognosticator in muscle-invasive bladder cancer.
abstract: BACKGROUND
  The prognosis of muscle-invasive bladder cancer is poor. Molecular prognosticators have gained increasing attention for individualized therapeutic options because they can identify patients with different prognoses.
  
  
  METHODS
  Tissue microarrays of formalin-fixed and paraffin-embedded tumor samples from 206 bladder cancer patients treated with cystectomy and chemotherapy were studied for SNAI1 protein expression by immunohistochemistry. SNAI1 expression was evaluated using an immunoreactive score (IRS). For statistical analysis, the patients were separated into two groups: those with tumor specimens negative for SNAI1 expression (IRS = 0), and the other positive for SNAI1 expression (IRS ≥1).
  
  
  RESULTS
  Tumor samples from 42 patients showed negative SNAI1 expression, whereas the nuclei of tumor cells from 164 patients showed detectable nuclear staining of SNAI1. A Kaplan-Meier analysis of the bladder cancer patients with negative SNAI1 expression showed significantly reduced disease-specific survival (DSS) and progression-free survival (PFS) compared to the patients with positive expression (p = 0.010 and 0.013). A multivariate Cox regression analysis (adjusted for gender, age, tumor stage, tumor grade, lymph node metastasis, chemotherapy, and histologic subtype) again showed a significant correlation between patients lacking SNAI1 expression and DSS (p = 0.005; relative risk 2.31; 95 % confidence interval 1.28-4.17) or PFS (p = 0.004; relative risk 2.20; 95 % confidence interval 1.29-3.78) compared to patients with positive SNAI1 staining.
  
  
  CONCLUSIONS
  Loss of SNAI1 protein expression is an independent prognosticator for PFS and DSS in bladder cancer patients treated by radical cystectomy and adjuvant chemotherapy. Its prognostic value for neoadjuvant or adjuvant chemotherapy must be evaluated in further prospective randomized controlled trials.
authors.affiliation: Department of Urology, University Hospital Erlangen, Erlangen, Germany. bastian.keck@uk-erlangen.de
authors.forename: Bastian
authors.initials: B
authors.lastname: Keck
authors.forename: Sven
authors.initials: S
authors.lastname: Wach
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Goebell
authors.forename: Frank
authors.initials: F
authors.lastname: Kunath
authors.forename: Simone
authors.initials: S
authors.lastname: Bertz
authors.forename: Jan
authors.initials: J
authors.lastname: Lehmann
authors.forename: Michael
authors.initials: M
authors.lastname: Stöckle
authors.forename: Helge
authors.initials: H
authors.lastname: Taubert
authors.forename: Bernd
authors.initials: B
authors.lastname: Wullich
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000378:metabolism / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D015653:Cystectomy / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D019042:Muscle Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D000071250:Snail Family Transcription Factors; D015996:Survival Rate; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology / Q000628:therapy
chemical_list: D014408:Biomarkers, Tumor; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors